Abstract:
Anthracyclines, a class of drugs considered as most effective anticancer drugs, used in the various regimens of cancer chemotherapy, induce long-term impairment of mitochondrial respiration, increase reactive oxygen species, and induce other mechanisms potentially leading to neurotoxicity. According to literature findings, one drug of this class - doxorubicin used to treat e.g. breast cancer, bladder cancer, lymphoma, and acute lymphocytic leukemia may induce such effects in the nervous system. Doxorubicin has poor penetration into the brain due to the lack of drug penetration through the blood-brain barrier, thus the toxicity of this agent is the result of its peripheral action. This action is manifested by cognitive impairment and anatomical changes in the brain and peripheral nervous system found in both preclinical and clinical studies in adult patients. Furthermore, more than 50% of children with cancer are treated with anthracyclines including doxorubicin, which may affect their nervous system, and lead to lifelong damage in many areas of their life. Despite ongoing research into the side effects of this drug, the mechanism of its neurotoxicity action on the central and peripheral nervous system is still not well understood. This review aims to summarize the neurotoxic effects of doxorubicin in preclinical (in vitro and in vivo) research and in clinical studies. Furthermore, it discusses the possible mechanisms of the toxic action of this agent on the nervous system.
摘要:
蒽环类药物,一类被认为是最有效的抗癌药物的药物,用于各种癌症化疗方案,诱导线粒体呼吸的长期损害,增加活性氧,并诱导其他可能导致神经毒性的机制。根据文献发现,此类药物之一-阿霉素用于治疗例如乳腺癌,膀胱癌,淋巴瘤急性淋巴细胞白血病可能会在神经系统中引起这种作用。由于缺乏通过血脑屏障的药物渗透,阿霉素进入大脑的渗透性较差,因此,这种药物的毒性是其外周作用的结果。这种作用表现为在成年患者的临床前和临床研究中发现的认知损害和大脑和周围神经系统的解剖学变化。此外,超过50%的癌症患儿接受了蒽环类药物治疗,包括阿霉素,这可能会影响他们的神经系统,并导致他们生活中许多领域的终身损害。尽管正在对这种药物的副作用进行研究,其对中枢和周围神经系统的神经毒性作用机制尚不清楚。本文旨在总结阿霉素在临床前(体外和体内)研究和临床研究中的神经毒性作用。此外,它讨论了这种药物对神经系统的毒性作用的可能机制。